Clinical usefulness of virulence factors of Helicobacter pylori as predictors of the outcomes of infection. What is the evidence?
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Adhesins, Bacterial↗
Biomedical subjects
G Capellá
Publications and source records attributed to G Capellá.
Immortalized bovine pancreatic duct cells become tumorigenic after transfection with mutant k-ras.
Mutation of the K-ras gene is thought to be an early and important event in pancreatic carcinogenesis. In order to study the role of this molecular alteration in the transition from the normal to the neoplastic pancreatic cell, bovine pancreatic duct cells were first immortalized by SV40 large T antigen (Ag) complementary (c)DNA transfection and then transfected with a mutated K-ras gene. As did primary duct cells, the immortalized duct cells (more than 100 passages) expressed cytokeratins, carbonic anhydrase type-II, cystic fibrosis transmembrane conductance regulator (CFTR), and multidrug resistance (mdr). They grew as a single layer after transplantation under plastic domes and formed three-dimensional structures resembling ducts when grown on Matrigel. Cell growth was stimulated by insulin, epidermal growth factor (EGF), transforming growth factor (TGF)-alpha, but cells did not respond to gastrin and CCK-8. They did not form colonies in soft agar nor did they form tumors in nude mice. Immortalized cells transfected with mutated K-ras acquired the ability to form tumors after orthotopic injection into the nude mouse pancreas. It is concluded that SV 40 immortalized bovine pancreatic
Animals↗
p53 and K-ras mutations in pancreatic juice samples from patients with chronic pancreatitis.
BACKGROUND: Mutations in p53 and ras genes are frequent in pancreatic carcinoma. Several ras mutations are consistently detected in the pancreatic juice from patients with chronic pancreatitis. The p53 gene mutations have been detected occasionally in chronic pancreatitis tissue. It was the aim of this study to evaluate the presence and clinical significance of p53 and ras mutations in clinical pancreatic juice samples from patients with chronic pancreatitis. METHODS: Pancreatic juice was obtained from 66 patients with chronic pancreatitis and no evidence of pancreatic carcinoma (51 men, 15 women; age 17-86 years [mean 49.6 +/- 12.9]). Patients were followed prospectively for 26 +/- 3 (4-54) months. Detection of p53 gene mutations was by temperature gradient gel electrophoresis (TGGE) and single strand conformation polymorphism (SSCP) for exons 5-8. Analysis of ras mutations was performed by SSCP/polymerase chain reaction, restriction fragment length polymorphism/polymerase chain reaction. All mutations were confirmed by sequencing. RESULTS: Five of 66 (7.5%) pancreatic juice samples contained p53 mutations, and ras mutations were detected in 6 cases (9%). Cytology was negative in all cases. No pancreatic carcinoma developed during follow-up and neither cancer cells nor preneoplastic lesions could be detected histologically in resected specimens. Although no correlation between p53 mutations and duration of pancreatitis or drinking habits was found, K-ras mutations correlated with both heavy smoking and severity of the disease. CONCLUSION: p53 and ras mutations can be detected in a minority of pancreatic juice samples from patients with chronic pancreatitis in the absence of malignancy.
Adolescent↗
DCC and SMAD4 alterations in human colorectal and pancreatic tumor dissemination.
Chromosome 18q is lost a high proportion of colorectal and pancreatic cancers. Three candidate tumor suppressor genes, DCC, Smad4 and Smad2 have been identified in this chromosome region. DCC and Smad4 aberrations have been previously identified in pancreatic and colorectal tumors. The aim of this study was to compare the presence of concurrent genetic aberrations in DCC and neighboring Smad4 and Smad2 genes during colorectal and pancreatic distal dissemination. We have used a panel of orthotopically implanted colorectal and pancreatic xenografts and corresponding metastases. We have shown that while LOH at DCC locus occurred at a similar frequency in both tumors, diminished DCC protein expression was exclusively present in colorectal tumors harboring intragenic DCC LOH. In contrast, in pancreatic xenografts loss of DCC protein and mRNA expression was restricted to metastases. Smad4 gene aberrations were detected at a similar frequency in both tumors and were selected for during distal dissemination. Acquisition of alterations in both genes occurred independently. Our results suggest that both DCC and Smad4 contribute to pancreatic and colorectal distal dissemination. However, the role of DCC may differ between both tumor types.
Adenocarcinoma↗
A highly sensitive method for K-ras mutation detection is useful in diagnosis of gastrointestinal cancer.
Detection of molecular features such as K-ras mutations has been used to evaluate potential tumour markers in a wide variety of clinical samples. Here we have applied a recently developed highly sensitive method for detection of K-ras codon 12 mutations to colorectal and pancreatic cancer diagnosis. We analysed 67 faecal samples from patients undergoing diagnostic colonoscopy under suspicion of colorectal cancer. PCR products were obtained in 62 of 67 (93%) faecal samples. Mutations were detected in exfoliated cells in 6 of 22 (27%) of the adenomas and in 6 of 11 (55%) of adenocarcinomas. No false positives were observed. Agreement between faecal samples and corresponding tissues was 100% for adenocarcinomas and 65% for adenomas. Mutations were also analysed in 61 pancreatic fine-needle aspirates. Mutations were detected in 36 of 45 (80%) of the pancreatic aspirates diagnosed as pancreatic cancer without false positives. Our findings suggest that, when colorectal cancer is suspected, detection of K-ras codon 12 mutations in faecal samples using this new method is specific for colorectal tumours. Additionally, this technique is a good alternative for evaluation of pancreatic masses.
Adenocarcinoma↗
Orthotopic models of human pancreatic cancer.
Orthotopic transplantation of solid tumor fragments of human tumors in nude mice reproduces their pattern of local growth and distal dissemination. While lymphatic, hepatic or peritoneal dissemination can be reproduced, perineural invasion is absent. Early passages (less than 3) of xenografts show a high degree of stability regarding K-ras, p53 and p16 gene status. On the other hand, advanced passages of tumors acquire additional alterations in the p15 and Smad4 genes. Mutations in K-ras, p53, p15 and Smad4 genes can be acquired, in this model system, in the more advanced stages of pancreatic tumor dissemination. Finally, it is also possible to standardize local growth of these tumors as well as its dissemination pattern giving us a preclinical tool to evaluate the anticancer activity of new drugs.
Adenocarcinoma↗
Restriction fragment length polymorphism of the L-myc gene is not a prognostic factor in bladder cancer patients.
The L-myc restriction fragment length polymorphism has been suggested to be of prognostic significance in some types of primary tumours. We examined the prognostic and susceptibility significance of the L-myc genotype in a group of 98 bladder cancer patients. The L-myc genotype did not correlate with any pathologic parameter and does not offer any clinical utility in patients with bladder cancer.
Adolescent↗
Improved detection of K-ras codon 12 mutations in fecal exfoliated cells.
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Codon↗
[Molecular genetics of human pancreatic cancer].
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Cell Cycle↗
Disruption of the antiproliferative TGF-beta signaling pathways in human pancreatic cancer cells.
Resistance to TGF-beta1 occurred in pancreatic cancer cells suggesting that inactivation of TGF-beta inhibitory signaling pathways may play an important role in human pancreatic cancer. The aim of our study was to determine the presence of alterations in the main putative components of the TGF-beta inhibitory signaling pathways (p15, Smad4, Smad2, TGFbeta-RII, CDC25A). A panel of human carcinomas of the exocrine pancreas orthotopically implanted and perpetuated in nude mice and pancreatic cancer cell lines were studied. p15 gene alterations, mainly homozygous deletions that involved exons 1 and/or 2, were found in the 62.5% (5 of 8) of pancreatic xenografts whereas Smad4 gene aberrations were found in one of eight xenografts and in two of seven cell lines. Additional aberrations in these genes were acquired during in vivo perpetuation and distal dissemination. Paradoxically, TGFbeta-RII overexpression and a decrease in CDC25A protein levels were found in all tumors and cell lines. In one cell line, resistance to TGF-beta1 occurred in the absence of alterations in the genes analysed so far. We conclude that all human pancreatic tumor cells analysed herein have non-functional TGF-beta pathways. The majority of cells harbor alterations in at least one of the putative components of TGF-beta pathways, mainly in p15 and Smad4 genes. These results suggest that inactivation of TGF-beta signaling pathways plays an important role in human pancreatic tumorigenesis.
Animals↗
K-ras gene mutations in the diagnosis of fine-needle aspirates of pancreatic masses: prospective study using two techniques with different detection limits.
Detection of K-ras mutations may be useful in the evaluation of pancreatic cancer. The aim of this study was to assess, in a prospective design, the diagnostic utility of K-ras mutation analysis in 62 consecutive fine-needle aspirates of pancreatic masses, using two PCR-based techniques-standard and enriched-with detection limits of a mutant allele in the presence of 10(2) or 10(3) wild-type alleles, respectively. Cytology alone offered a diagnostic sensitivity of 75%. The enriched higher sensitivity detection technique, in combination with cytology, offered a diagnostic sensitivity of 91% without false positives. The molecular analysis would have contributed to diagnosis in an additional 14 cases of pancreatic cancer. The standard technique contributed to diagnosis in an additional 9 cases. These results strongly support the use of the enriched method of detecting K-ras mutations as a complement to cytology in the evaluation of pancreatic masses.
Aged↗
Orthotopic xenografts of human pancreatic carcinomas acquire genetic aberrations during dissemination in nude mice.
Orthotopic transplantation of human tumors in nude mice reproduces the pattern of local growth and distal dissemination. The aim of our study was to determine the pattern of genetic alterations in human carcinomas of the exocrine pancreas orthotopically implanted and perpetuated in nude mice. Eight of the sixteen orthoimplanted human pancreatic carcinomas were perpetuated through several passages. Four perpetuated tumors followed distinct patterns of distal dissemination. Point mutations in the K-ras gene, genetic aberrations in the p53 and p16 genes, and allelic losses at retinoblastoma, adenomatous polyposis coli, and deleted in colorectal cancer loci were analyzed. Perpetuated tumors maintained the pattern of genetic alterations present in primary tumors. Five perpetuated tumors contained K-ras mutations, and all tumors contained p53 and/or p16 genetic aberrations. Allelic losses were present in four of the perpetuated tumors. Additional genetic alterations were detected in 6 of 35 metastases analyzed. Five of 9 peritoneal metastases or malignant ascitic cells acquired either K-ras or second p53 mutations. In contrast, only 1 of 25 liver metastases and none of the lymph node metastases acquired additional mutations. No additional p16 gene aberrations or other allelic losses were evidenced during tumor dissemination. We conclude that orthotopically implanted pancreatic carcinomas xenografted in nude mice show a high degree of genetic stability. Mutations in K-ras and p53 genes can occur in this model system in the more advanced stages of pancreatic tumor progression, mainly during peritoneal dissemination.
Adenocarcinoma↗
Diagnostic utility of K-ras mutations in fine-needle aspirates of pancreatic masses.
BACKGROUND & AIMS: Mutations at codon 12 of the K-ras gene are present in 65%-100% of carcinomas of human exocrine pancreas and could be used as a potential tumor marker at the tissue level. The purpose of this study was to assess, in large series of patients, the utility of K-ras mutation analysis to evaluate fine-needle aspirates of pancreatic masses. METHODS: One hundred fifteen fine-needle aspirates obtained from 93 patients were evaluated retrospectively. Cytological analysis was based on the review of cell blocks. Mutations were detected by using artificial restriction fragment length polymorphisms using the Hphl and BstNl approaches. RESULTS: The sensitivity and specificity of cell block cytology was 64% and 100%, respectively, for the diagnosis of pancreatic carcinoma. K-ras mutations were detected in 41 pancreatic carcinomas (sensitivity, 59%) and in one mucinous cystic tumor; specificity of ras analysis alone was 100%. The sensitivity of cytology combined with K-ras mutations were 77.6% and 100%, respectively. CONCLUSIONS: The detection of K-ras mutations would have suggested the diagnosis of pancreatic cancer in 14 cases otherwise not detected by cytology alone. K-ras mutation analysis should be restricted to cell blocks containing suspicious, normal-appearing duct cells, or insufficient material in the cytological examination.
Aged↗
[Molecular changes in adenocarcinoma of the small intestine associated with Peutz-Jeghers syndrome].
The presence of molecular alterations in the c-K-ras and p53 genes in a small bowel adenocarcinoma arising in a case of Peutz-Jeghers syndrome is reported. The absence of mutations at codon 12 and 13 of the c-K-ras gene in the hamartoma and carcinoma indicates that this oncogene does not contribute to its development. On the other hand, p53 protein overexpression was detected in a small proportion (5-10%) of adenocarcinoma cells. Our findings suggest that p53 inactivation occur in late stages of tumour progression.
Adenocarcinoma↗
K-ras and p53 mutations in hamster pancreatic ductal adenocarcinomas and cell lines.
K-ras and p53 gene alterations are frequently found in human pancreatic carcinomas and cell lines. The aim of this study was to analyze for the presence of K-ras and p53 gene mutations in hamster pancreatic tumors and cell lines. Mutations at the first coding exon of the K-ras gene and in exons V to VIII of the hamster p53 gene were analyzed in six cell lines (H2T, PC1, PC1.2, PC1.0, WD, and PD) and in N-nitroso-bis(2-oxopropyl)amine-induced pancreatic (n = 9) and extra-pancreatic (n = 4) tumors. K-ras mutations were present in seven of the nine pancreatic tumors and in all extra-pancreatic tumors. No p53 mutations were detected in the tumors. All cell lines analyzed contained K-ras mutations. Moreover, four of the six cell lines contained single amino acid substitutions in the p53 gene. Cell lines derived from nitrosamine-induced pancreatic tumors in the hamster contained K-ras and p53 alterations similar to those found in cell lines derived from human pancreatic carcinomas.
Animals↗
Expression of somatostatin in rat pineal cells in culture.
The expression of somatostatin mRNA was investigated in rat pineal cells after 1 week in culture, using reverse transcription of mRNA into cDNA and the polymerase chain reaction. The positive expression in cultured pineal cells demonstrates the capacity of this gland to synthesize somatostatin in denervated cells. Thus, apart from the neural origin of pineal somatostatin, which has been described in detail in the bovine species, a parenchymal source is demonstrated.
Animals↗
[Nutritional status and cephalic duodenopancreatectomy in neoplasm treatment].
Usually, nutritional status of patients with neoplasia is poor. This is an important factor when the radical resection of the tumor implies aggressive surgery, and it has a clear influence on postoperative morbidity and mortality. From 1979 to 1988, 33 cephalic duodenopancreatectomies for carcinoma of the ampullary region have been carried out in the Servicio de Cirugía Digestiva, hospital "Santa Cruz y San Pablo". For retrospective evaluation of postoperative parenteral nutrition patients have been divided in two groups: group A, with routine parenteral nutrition and group B, with parenteral nutrition only if required. In group A, 75% of patients did not present postoperative morbidity, compared to 38% of patients in group B. There were 7 deaths: all of them in group B. The time of hospitalization was lower in group A. Differences in the three parameters under consideration was statistically significant. We conclude that, in order to improve morbidity and mortality as well as to reduce the hospitalization time, postoperative parenteral nutrition is necessary in patients submitted to cephalic duodenopancreatectomy for neoplasia.
Aged↗
The influence of age on early surgical treatment of acute cholecystitis.
This study was undertaken to assess the influence of age on the early surgical treatment of acute cholecystitis. One hundred consecutive patients who had early operations for acute cholecystitis were divided into two groups according to age. Group 1 consisted of 41 patients who were younger than 60 years of age, and group 2 was made up of 59 patients who were more than 60 years of age. Shock, leukocytosis, hyperglycemia and uremia were more common in those patients in group 2 (p less than 0.05). The over-all diagnostic effectiveness was 94 per cent. The mortality rate was 4.1 per cent (n = 4). There were no significant differences in morbidity and mortality between both groups. In conclusion, advanced age is not a contraindication for early surgical treatment of acute cholecystitis.
Acute Disease↗